rs1803167

Variant names:

• chr2-135911179-G-A
• rs1803167
• NM_001349.4:c.1374C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-135911179-G-A
• chr2-135911179-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001349.4(DARS1):​c.1374C>T​(p.Ser458Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S458S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DARS1 NM_001349.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 0 publications found

Genes affected

DARS1 (HGNC:2678): (aspartyl-tRNA synthetase 1) This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyelination with brainstem and spinal cord involvement and leg spasticity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DARS1 Gene-Disease associations (from GenCC):

• hypomyelination with brain stem and spinal cord involvement and leg spasticity

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=1.97 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DARS1	NM_001349.4	c.1374C>T	p.Ser458Ser	synonymous_variant	Exon 15 of 16	ENST00000264161.9	NP_001340.2
DARS1	NM_001293312.1	c.1074C>T	p.Ser358Ser	synonymous_variant	Exon 14 of 15		NP_001280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DARS1	ENST00000264161.9	c.1374C>T	p.Ser458Ser	synonymous_variant	Exon 15 of 16	1	NM_001349.4	ENSP00000264161.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1397414 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 699300

African (AFR) AF: 0.00 AC: 0 AN: 32104

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 39320

South Asian (SAS) AF: 0.00 AC: 0 AN: 84818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053830

Other (OTH) AF: 0.00 AC: 0 AN: 58154

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		2.0
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1803167; hg19: chr2-136668749;